Emerging strategies to fabricate polymeric nanocarriers for enhanced drug delivery across blood-brain barrier: An overview

Blood-brain barrier (BBB) serves as an essential interface between central nervous system (CNS) and its periphery, allowing selective permeation of ions, gaseous molecules, and other nutrients to maintain metabolic functions of brain. Concurrently, it restricts passage of unsolicited materials from bloodstream to CNS which could otherwise lead to neurotoxicity. Nevertheless, in the treatment of neurodegenerative diseases such as Parkinson's, Alzheimer's, diffuse intrinsic pontine glioma, and other brain cancers, drugs must reach CNS. Among various materials developed for this purpose, a few judiciously selected polymeric nanocarriers are reported to be highly prospective to facilitate BBB permeation. However, the challenge of transporting drug-loaded nanomaterials across this barrier remains formidable. Herein a concise analysis of recently employed strategies for designing polymeric nanocarriers to deliver therapeutics across BBB is presented. Impacts of 3Ss, namely, size, shape, and surface charge of polymeric nanocarriers on BBB permeation along with different ligands used for nanoparticle surface modification to achieve targeted delivery have been scrutinized. Finally, we elucidated future research directions in the context of designing smart polymeric nanocarriers for BBB permeation. This work aims to guide researchers engaged in polymeric nanocarrier design, helping them navigate where to begin, what challenges to address, and how to proceed effectively.